Mouse F1 spleen cells can develop cytotoxic effector cells in vitro directed against parental cells. The antigenic differences detected appear to be controlled by a structural gene (Hh-1) mapping in or near the D region of the H-2 complex. Although a number of positive correlations have been demonstrated between murine hemopoietic graft rejection in vivo and F1 anti-parent cytotoxicity in vitro, certain differences have been recently found between these two F1 anti-parent reactions. These include the observations that marrow graft rejection does not require priming and is not dependent upon thymus-dependent cells, whereas the development of cytotoxic cells requires sensitization and is effected by T-lymphocytes. Furthermore, the cytotoxic effector cells appear to require the recognition of more than Hh-1, possibly other self antigens associated with cytotoxic function. Comparisons were also made between natural killer (NK) cell activity and F1 anti-parent marrow rejection in vivo and cytotoxic activity in vitro. A number of parallels were observed among NK cell activity, F1 anti-parent marrow graft rejection in vivo, and F1 anti-parent cytotoxicity in vitro. BIBLIOGRAPHIC REFERENCES: Shearer, G. M., Cudkowicz, G., and Garbarino, C. G.: In vitro induction of F1 hybrid anti-parent cell-mediated cytotoxicity. J. Immunol. 117: 754-759, 1976. Shearer, G.M., Waksal, H., Cudkowicz, G.: An in vitro model of hybrid resistance to bone marrow grafts. Transplant. Proc. 8: 469-475, 1976.